Acquired immunodeficiency syndrome (AIDS) is associated with a viral (HIV-I) mediated progressive depletion of the helper/inducer T4+ T cell subset, whereas acute T cell leukemia (ATL) is associated with viral (HTLV-I) mediated growth of the same T cell subset. To better understand the host cell effects on viral replication, we have developed in vitro cell line models to study latency of both HTLV-I and HIV. Examination of HTLV-I infected B cells from ATL patients has shown the virus to be latent in these cells. No viral mRNAs are being transcribed yet the integrated provirus is functional and can be activated to transform other T and B cells. When the virus infects T-cells, the virus is expressed; when it infects B cells, it is not expressed. In addition, the macrophage, know to be infected in AIDS patients was examined for ability to restrict HIV-I expression. THP-1, a macrophage cell line derived from a patient with monocytic leukemia, was permissive for HIV-I expression. However, these infected cells become naturally latent for HIV 4-6 weeks after infection. HIV-I and HTLV-I are among a class of viruses that have a unique mechanism of stimulating viral transcription. Both viruses make proteins which act in trans to positively regulate viral transcription. Studies of the transactivation mechanism in both of these latently infected cultures showed that transactivation of viral transcription is markedly inhibited. This indicates that the host factors play a role in this transcription and these cell either are deficient in positive regulators or possess negative regulators of viral transcription.